IntroductionCTLA-4 insufficiency is the rare immunodeficiency described in literature by different clinical presentations and variety of identified mutations. Majority of described cases developed symptoms in second or third decades of life. We would like to present our experience with four cases of early childhood presentation of CTLA-4 insufficiency. Between 2015 and 2022 we treated four children from 3 families, who were referred to Department of Pediatric Hematology, Oncology and Transplantology because of cytopenia. Cases presentationThe demographical and clinical data of our patients are presented in table attached. Discussion and conclusionAccording to recent report (JACI, 2022) about the 173 patients carrying a CTLA-4 pathogenic variant median age of symptom onset was 13 years and median age of diagnoses of CTLA-4 insufficiency was 24 years and only few patients were below age of 5 at the time of presentation. Clinical manifestations in our patients were predominantly hematological, so we concluded that autoimmune cytopenia presented in two or more lines in early childhood should be screened for inhereditary immune dysregulation i.e. CTLA-4 insufficiency. Available treatment is effective in short time observation but long term outcome of these pediatric patients is unknown.Table(abstract 142) Clinical presentation of padiatric patients with CTLA-4 insufficiency treated in one centerPatient 1Patient 2Patient 3Patient 4SexMFMMAge at first symptoms presentation4 years9 months21 monthsBrother of pts 3.Screened after birthAge at diagnosis6 years18 months2,5 years2 monthsPathogenic CTLA-4 geneCTLA4CTLA4CTLA4CTLA4variantc.356T>Cc.515C>Tc.118G>Ac.118G>AClinical presentationThrombocytopenia followed by pancytopenia and finally hepatosplenomegaly, fever and colitisLeukopenia and granulocytopenia, anemia, hepatosplenomegalyThrombocytopenia and agranulocytosisNo symptomsHypogammaglobulinemia TreatmentNoNoNoNoSteroides, ATG followed by HLH protocol (Dexamethason, CsA and Etoposide) and HSCTsirolimussirolimusNo treatmentOutcomeAlive and well, without treatmentAlive and well on sirolimusAlive and well on sirolimusAlive, watch and wait strategyFollow up time5 years from diagnosis, 4 years postHSCT2,5 years from start of sirolimus2,5 years from start of sirolimus6 months